Parental gamma irradiation induces reprotoxic effects accompanied by genomic instability in zebrafish (Danio rerio) embryos

Hurem, Selma; Gomes, Tânia; Brede, Dag Anders; Hansen, Elisabeth Lindbo; Mutoloki, Stephen; Fernández, C. H. Zepeda; Mothersill, Carmel; Salbu, Brit; Kassaye, Yetneberk A.; Olsen, Ann‐Karin; Oughton, Deborah; Aleström, Peter; Lyche, Jan Ludvig

doi:10.1016/j.envres.2017.07.053

Cited by 40 publications

(52 citation statements)

References 67 publications

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“…This would seem to be a consequence of an effect inherited from the parents. Results were similar to those observed in other exposure conditions (dose rate, recovery duration) by Hurem et al (2017a). Because no effect was observed in 10-d larvae, the oxidative stress induced by gamma irradiation seems to be transitory.…”

Section: Ros Production and Genotoxicity After Irradiated And Recoversupporting

confidence: 88%

Adverse effects induced by chronic gamma irradiation in progeny of adult fish not affecting parental reproductive performance

Noëmie

Gagnaire

Frelon

et al. 2019

Enviro Toxic and Chemistry

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Multigenerational studies have become of great interest in ecotoxicology since the consequence of parental exposure to contaminants on offspring generations was established in situ or in laboratory conditions. The present study mainly examined the chronic effects of external Cs‐137 gamma irradiation exposure at 4 dose rates (control, 0.5, 5, and 50 mGy h–1) on adult zebrafish (F0) exposed for 10 d and their progeny (F1) exposed or unexposed for 4 to 5 d. The main endpoints investigated included parental reproductive performance, embryo‐larval survival, DNA alterations, and reactive oxygen species (ROS) production in F0 and F1. No effects on reproductive success, fecundity, or egg fertilization rate were observed. However, drastic effects were observed on F1 exposed to 50 mGy h–1, resulting in a mortality rate of 100%. The drastic effects were also observed when the progeny was not irradiated. It was demonstrated that the sensitivity of the embryos was mainly attributable to parental irradiation. Moreover, these drastic effects induced by adult irradiation disappeared over time when 10 d–irradiated adults were placed in a nonirradiated condition. Alterations in larval DNA were observed for the 3 dose rates, and an increase of ROS production was also shown for the 2 lowest dose rates. The present study improves our understanding of the consequences of parental exposure conditions to the progeny. Furthermore, it provides an incentive to take transmitted generational effects into account in ecological risk assessments. Environ Toxicol Chem 2019;38:2556–2567. © 2019 SETAC

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Section: Ros Production and Genotoxicity After Irradiated And Recoversupporting

confidence: 88%

Adverse effects induced by chronic gamma irradiation in progeny of adult fish not affecting parental reproductive performance

Noëmie

Gagnaire

Frelon

et al. 2019

Enviro Toxic and Chemistry

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“…5793. AB wildtype zebrafish were maintained according to standard operating procedures with 28 °C and photoperiod of 10 h dark and 14 h light as described earlier [47].…”

Section: Zebrafish Husbandrymentioning

confidence: 99%

Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish

Broeder

Ballangby

Kamminga

et al. 2020

Epigenetics & Chromatin

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Background: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. Results:Zebrafish embryos (0-5 days post-fertilization, dpf ) exposed to non-toxic concentrations of PF-06726304 acetate (5 μM) and TBT (1 nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf ). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. Conclusions:Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.

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“…It is important to be aware that different setups require different approaches. For thin specimens exposed in air (such as plants) it is necessary to consider buildup conditions (or the lack thereof); for larger organisms in air (like mice) we may want to calculate whole-body absorbed dose rates for different orientations and positions of the animals in their cages and estimate an average (Graupner et al 2017); and for setups with soil or water habitats, we need to account for the variation in absorbed dose rates with depth due to attenuation and scattering in the media (Hurem et al 2017). Geant4 simulations are useful in all these cases, but are limited by the ease and accuracy by which setups can be modelled.…”

Section: Discussionmentioning

confidence: 99%

“…Because such simulations cannot be directly validated without resorting e.g. to calorimetry, we instead validate simulations of the absorbed dose to water at a point, by modelling a 9 L aquarium for which we have measurements of the absorbed dose rate to water at a depth of 7.5 cm from previous work (Hurem et al 2017).…”

Section: The Geant4 Figaro Modelmentioning

confidence: 99%

“…In lieu of validating simulations of whole-system or wholebody absorbed dose rates, we validate simulations of the absorbed dose rate to water at a point by modelling a 9 L aquarium for which we have measured the absorbed dose rate to water at a depth of 7.5 cm in previous work to 54 ± 2 mGy/h (Hurem et al 2017). Based on current best estimates for the strengths of the modelled sources, the simulated value was 53.6 mGy/h.…”

Section: Simulated Absorbed Dose Rates To Watermentioning

confidence: 99%

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A framework for exposure characterization and gamma dosimetry at the NMBU FIGARO irradiation facility

Hansen

Lind

Oughton

et al. 2018

International Journal of Radiation Biology

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Purpose: The FIGARO low dose 60 Co gamma irradiation facility at the Norwegian University of Life Sciences, Ås, Norway, is dedicated to the study of effects on living organisms from acute or chronic ionizing radiation exposures, either alone or in combination with other stressors such as UV radiation, metals or radionuclides. Here, we present a framework of working guidelines and computer software for characterization of absorbed dose rates and accumulated doses to organisms exposed within the continuous gamma field at FIGARO. The aims of the framework are to ensure gamma exposures are well characterized, that results from exposures are correctly interpreted in terms of absorbed dose rates and accumulated doses, and that sufficient information is available so that exposures can be reproduced later or at other facilities. Methods: The software of the framework includes a Geant4 application for Monte Carlo radiation transport simulations and tools for dose planning, recording and reporting. The working guidelines are prepared for expert users who provide simulated, calculated or estimated absorbed dose rates and for regular users who conduct exposure experiments and are responsible for record keeping. To demonstrate the developed framework, we use a case study where 14 freshwater microcosms are exposed to four levels of gamma dose rates at FIGARO. Conclusion: The framework guides users towards good dosimetry practices. Lessons learned could be transferable to other gamma irradiation facilities.

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Parental gamma irradiation induces reprotoxic effects accompanied by genomic instability in zebrafish (Danio rerio) embryos

Cited by 40 publications

References 67 publications

Adverse effects induced by chronic gamma irradiation in progeny of adult fish not affecting parental reproductive performance

Adverse effects induced by chronic gamma irradiation in progeny of adult fish not affecting parental reproductive performance

Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish

A framework for exposure characterization and gamma dosimetry at the NMBU FIGARO irradiation facility

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